Negative regulation of the expressions of cytokeratins 8 and 19 by SLUG repressor protein in human breast cells

作者：Tripathi MK; Misra S; Chaudhuri G^*

来源：Biochemical and Biophysical Research Communications, 2005, 329(2): 508-515.

DOI：10.1016/j.bbrc.2005.02.006

• invasiveness
• breast tumor
• SLUG
• cytokeratin 8
• cytokeratin 19
• metallothionein IG
• metallothionein IL
• siRNA
• microarray

Invasiveness of tumor cells is often determined by the profile of their expressed genes. To determine the gene expression differences between an invasive and a non-invasive human breast tumor Cells, we selected BT-549 (invasive) and MDA-MB-468 (non-invasive) cells, and compared their transcriptomes by cDNA microarray analysis. Among the significant differences in gene expressions, notable are the up-regulation of cytokeratins 8 and 19, and down-regulation of metallothioneins 1G and 1L in MDA-MB-468 cells. Since MDA-MB-468 cells do not express SLUG, a member of a small family of E2-box-binding zinc finger silencer proteins, we studied whether the cytokeratin gene overexpressions in these cells are due to the absence of SLUG. Inducible expression of SLUG in MDA-MB-468 cells inhibited the expressions of the cytokeratin 8 and 19 but not others as was revealed by microarray analysis. Similarly, siRNA knock down of SLUG in BT-549 cells increased the expressions of those cytokeratin mRNAs. SLUG levels in the cell regulated the function of cytokeratins 8 and 19 gene promoters. We conclude that the expressions of cytokeratins and metallothioneins may be associated with the differential invasive behaviors of these breast tumor cells and SLUG may have regulatory roles in this process.

• 出版日期2005-4-8